Autoimmune diseases such as multiple sclerosis (MS), rheumatoid arthritis, lupus, and type 1 diabetes result from the recognition and attack of self-tissues or organs by the host immune system. In the case of MS, the immune system attacks the myelin sheath of the neurons causing disruption of the signal translation in the central nervous system (CNS). Without the protection of the myelin sheath proteins, nerve impulses are either disrupted or slowed down. While the triggers of MS have not been clearly elucidated, several factors such as Epstein-Barr virus (EBV) infection, genetic predisposition, and environmental effects are thought to play roles in its development. Just as in rheumatoid arthritis and type 1 diabetes, MS results from activation of a subpopulation of self-recognizing T cells that demyelinate the nerve fibers in CNS.
One of the potential ways that T-cells recognize the myelin sheath is by activation of a subset of autoreactive T-cells, which recognize the self-myelin sheath. One possible mechanism of activation of a subpopulation T-cell is via formation of the “immunological synapse” at the interface between T-cells and antigen-presenting cells (APC). The immunological synapse is a “bull's eye”-like structure that is composed of a cluster of interactions between T-cell receptors (TCR) and major histocompatibility complex-peptide (MHC-p) at the center (signal 1) and a cluster of interactions between co-stimulatory molecules (i.e., signal 2, B7/CD28, ICAM-1/LFA-1) at the periphery of the bull's eye. The differentiation of naïve T-cells to a specific subset (i.e., Th1, Th2, Th17, T-reg) depends on the type of co-stimulatory signal delivered. Blocking signal 2 during this process could lead to immune unresponsiveness of T cells called anergy. Inhibition of ICAM-1/LFA-1 (signal 2) interaction suppresses Th1-type immune response and could promote a non-inflammatory suppressor and/or regulatory T cells.
While no cure currently exists for MS and many other autoimmune disorders, many of today's therapies, including biologic drugs such as such as interferons (Avonex®, Betaseron®), antibodies (Tysabri®), and antineoplastics (mitoxantrone), focus on slowing down and altering the disease progression. Potential drugs such as monoclonal antibodies (mAb) or small molecules that block signal 2 have been developed for treating autoimmune diseases. Unfortunately, as a potential side effect, these drugs may suppress the general immune response and compromise the ability of the host to respond to pathogenic infections.